RNA Interference
RNA interference (RNAi) is currently used frequently in life science research, and its utility is widely recognized. RNAi indicates a phenomenon whereby mRNA is degraded sequence-specifically by double-stranded RNA, resulting in suppression of the expression of a gene. In the time since it was reported in 2001 that low-molecular double-stranded RNA of 21 bases can mediate RNAi in mammalian cells (Non-patent Reference 1), siRNA (small interference RNA) has been utilized often as a means of suppressing the expression of a target gene. siRNA is expected to be applied to pharmaceuticals and to be applied to the treatment of various refractory diseases, including cancer.
miRNA
miRNA (micro RNA) is an endogenous non-coding RNA of about 20-25 bases encoded on the genome. miRNA is first transcribed as a primary transcript (primary miRNA; referred to hereinafter as “pri-miRNA”) of several hundred to several thousand bases in length from a miRNA gene on the genomic DNA, then processed to become pre-miRNA (precursor miRNA) having a hairpin structure of approximately 60-70 bases. It then moves from the nucleus into the cytoplasm and is further processed to become double-stranded mature miRNA of about 20-25 bases. One of the strands of the double-stranded mature miRNA forms a complex with a protein called RISC (RNA-induced silencing complex) and is known to act to inhibit translation of a target gene by acting on the mRNA of the target gene (Non-patent Reference 1). More than 1000 types of miRNA are known in humans, mice, and the like. Each regulates the expression of multiple target genes and is suggested to participate in various life phenomena, such as cell growth, differentiation, and the like. For example, miRNA that participates in the differentiation of hematopoietic cells and neurons has been reported (Non-patent Reference 2). miRNA that participates in the growth of cancer cells has also been reported, and the use of the expression pattern of miRNA in the clinical diagnosis of cancer and methods of treating cancer by suppressing the growth of cancer cells by suppressing the expression of miRNA have been proposed (Patent References 1 and 2). mir582 is known as one of the miRNA (Non-patent Reference 3).
Bladder Cancer
Cancer of the bladder generally arises as a precancerous lesion and can change into invasive cancer. Some can also metastasize and grow. The most common bladder cancer is transitional cell carcinoma of epithelial origin, accounting for 90% of all bladder cancers. Surgical removal is possible for patients with superficial bladder malignancies, but the tendency for recurrence is strong. The five-year survival rate reduces to approximately 50% in the case of bladder malignancies that deeply invade the lower muscle tissue.
In any case, surgery is the main method of treatment of these bladder cancers. The extent of surgery is decided by the disease stage. Early-stage disease can generally be treated by intravesical chemotherapy and transurethral resection. Surgery is often combined with ancillary intravesical infusion of chemotherapeutics or immunotherapeutics to decrease the appearance of cancer at the same site as the bladder wall or other sites and to decrease the severity of recurrence. Definitive (radical) radiotherapy is generally used for bladder cancer patients for whom surgery is not indicated. In the case of superficial or low-malignancy disease, chemotherapy is performed directly within the bladder, the drug is caused to accumulate at the tumor site, and any tumor masses remaining after resection are removed. Systemic chemotherapy is also used for advanced bladder cancer.
Doxorubicin, epirubicin, and such anthracyclines are known to treat bladder cancer. Administration of anthracyclines is believed to reduce the risk of recurrence after surgery, but these compounds have systemic toxicity. This toxicity can be reduced by infusing the drug directly into the bladder, but the drug can enter other organ systems if any type of damage was done to the bladder by surgery. These compounds are also believed to have latent carcinogenicity regardless of the route of administration. It is therefore important to prevent the progression of invasive diseases and to develop safer treatment methods. Bladder cancer also characteristically has a relatively high recurrence rate despite surgical treatment or chemotherapy. The development of treatment methods that lower the recurrence rate is consequently demanded.